神经节苷酯联合丙种球蛋白治疗儿童重型病毒性脑炎的临床分析

【摘要】目的 探讨单唾液酸四已糖神节经苷酯(GM-1)联合大剂量丙种球蛋白(IVIG)治疗儿童重型病毒性脑炎(SVE)的临床效果。方法 将73例患儿随机分为3组,对照组25例,治疗A组24 例和治疗B组24例。对照组给予常规治疗,治疗A组在常规治疗基础上给予大剂量IVIG治疗,治疗B组在治疗A组基础上加用GM-1治疗。比较3组患儿临床症状消失时间、脑电图恢复正常时间、治疗前后血清神经元特异性烯醇化酶（NSE）及白细胞介素-6(IL-6)变化。结果 治疗A组、B组意识转清、惊厥控制、热退、头痛呕吐消失、肢体活动恢复、脑电图恢复正常时间及NSE、IL-6水平明显少于对照组（P＜0.05）;治疗A组、B组总有效率及显效率均明显高于对照组（P＜0.05）;治疗B组肢体活动恢复、脑电图恢复正常时间及NSE、IL-6水平明显低于治疗A组（P＜0.05）,治疗B组总有效率及显效率均明显高于治疗A组,差异均有统计学意义。两组在意识转清、惊厥控制、热退、头痛呕吐消失时间方面均无明显差异(P＞0.05);三组均无严重不良反应发生。结论 GM-1联合大剂量IVIG治疗小儿SVE有良好的临床疗效,值得临床推广应用。     

单唾液酸四己糖神经节苷脂钠注射液对新生儿缺氧缺血性脑病神经行为的影响

目的:观察单唾液酸四己糖神经节苷脂钠注射液对新生儿缺氧缺血性脑病(HIE)神经行为的影响及其临床疗效。方法:收集该院2009年10月～2011年10月2年间治疗的HIE患儿54例,HIE患儿随机分为常规治疗(A)组和单唾液酸四己糖神经节苷脂钠注射液治疗(B)组。对照两组的意识障碍、肌张力异常、原始反射异常的持续时间以及新生儿神经行为(NBNA)评分。统计分析两组的临床疗效。结果:意识障碍、肌张力异常、原始反射异常的持续时间A组显著长于B组(P<0.05),新生儿神经行为(NBNA)B组则显著高于A组(P<0.05)。A组显效7例,有效12例,无效8例,有效率为70.4%;B组显效14例,有效11例,无效2例,有效率为92.6%,统计学分析显示临床治疗有效率B组显著高于A组(P<0.05)。结论:单唾液酸四己糖神经节苷脂钠注射液治疗HIE患儿可以显著改善其神经行为的异常,临床疗效显著,值得临床推广应用。     

Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans

Several studies have successfully employed GM1 ganglioside to treat animal models of Parkinson's disease (PD), suggesting involvement of this ganglioside in PD etiology. We recently demonstrated that genetically engineered mice (B4galnt1^?/?) devoid of GM1 acquire characteristic symptoms of this disorder, including motor impairment, depletion of striatal dopamine, selective loss of tyrosine hydroxylase‐expressing neurons, and aggregation of α‐synuclein. The present study demonstrates similar symptoms in heterozygous mice (HTs) that express only partial GM1 deficiency. Symptoms were alleviated by administration of L‐dopa or LIGA‐20, a membrane‐permeable analog of GM1 that penetrates the blood–brain barrier and accesses intracellular compartments. Immunohistochemical analysis of paraffin sections from PD patients revealed significant GM1 deficiency in nigral dopaminergic neurons compared with age‐matched controls. This was comparable to the GM1 deficiency of HT mice and suggests that GM1 deficiency may be a contributing factor to idiopathic PD. We propose that HT mice with partial GM1 deficiency constitute an especially useful model for PD, reflecting the actual pathophysiology of this disorder. The results point to membrane‐permeable analogs of GM1 as holding promise as a form of GM1 replacement therapy. © 2012 Wiley Periodicals, Inc.     

联合应用神经生长因子和神经节苷脂1对坐骨神经损伤大鼠脊髓神经元的保护作用

目的：了解联合应用神经生长因子(NGF)和神经节苷脂1(GMl)对大鼠周围神经损伤后脊髓神经元的保护作用。方法：选用SD大鼠,分为生理盐水(NS)组、NGF组、GM1组和NGF GM1组,将大鼠坐骨神经造成5mm缺损,术中硅胶管内局部加药、术后大鼠损伤侧小腿肌注药物。术后定期光、电镜观察L4～I6脊髓前角神经元结构变化,测定损伤远段和近段神经传导速度。结果：脊髓运动神经元数目以及神经传导速度4周时,NGF组和GM1组均多于或快于NS组,NGF GM1组则多于或快于NS组、NGF组和GM1组,8周时NGF GM1组、NGF组、GM1组组间无显著性差异但均多于或快于NS组。结论：NGF GM1对周围神经损伤后脊髓运动神经元退变的保护作用与单用NGF或GM1相比,能更早期地发挥作用,并且效果优于单用NGF或GM1。     

外源性神经节苷脂对神经干细胞增殖分化的作用

目的：探讨外源性神经节苷脂（GM1）对从大鼠分离培养的神经干细胞（NSCs）增殖及分化的作用。方法：①利用无血清培养技术从胎鼠大脑皮质和海马分离培养原代细胞，加血清诱导其分化。（④在NSCs培养基和DMEM／F12培养基中加入不同浓度的GM1，观察GM1对NSCs增殖和分化的作用。结果：①与不含GM1的NSCs培养基相比，在NSCs培养基中加入低浓度的GM1，NSCs的生长无明显改变，随着GM1浓度的增加，NSCs克隆球体积逐渐减小，细胞逐渐死亡；②在DMEM／F12培养基中单独加GM1而不加血清，NSCs克隆球均未见继续生长，也未见分化，而是迅速的死亡。结论：①在NSCs培养基中，低浓度（12．5μg／m1）GM1对NSCs的增殖无明显影响，但较高浓度的GM1对NSCs的增殖有抑制作用。②DMEM／F12培养基中单独加GM1，而不加血清和其他生长因子，既不能诱导NSCs分化，也不利于NSCs的继续生长。     

Experimental autoimmune neuropathy with anti-GM1 antibodies and immunoglobulin deposits at the nodes of Ranvier

Summary Antibodies to GM1 or Gal(1–3)GalNAc are associated with motor or sensorimotor neuropathy and with motor neuron disease. To investigate the role of these antibodies in the neurological disorder, rabbits were immunized with GM1 or with Gal(1–3)GalNAc-BSA, and studied serologically, electrophysiologically and pathologically. Development of antibodies to the immunizing antigens was associated with a fall in the ratio of the amplitudes of the compound muscle action potential evoked by proximal versus distal stimulation of the sciatic nerve. Pathological studies revealed mild axonal degeneration and immunoglobulin deposits at the nodes of Ranvier in peripheral nerve, resembling those reported in a patient with motor neuropathy, motor conduction block and anti-GM1 antibodies. These studies provide evidence that anti-GM1 or anti-Gal(1–3)GalNAc antibodies cause conduction abnormalities and indicate that the antibodies may exert their effect, in part, by binding at the nodes of Ranvier in peripheral nerve.Supported by center grants from the Muscular Dystrophy Association and NINCDS (NS11766) to Columbia University. F.P. Thomas and S. A. Sadiq were fellows of the Muscular Dystrophy Association and the Charles A. Dana Foundation; F.P.Thomas is a fellow of the German Cancer Research Center (DKFZ)     

Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin

BACKGROUND: Detection of CDw60 in skin is representative of ganglioside D3 expression. This ganglioside is expressed primarily by melanocytes, and is of interest as a membrane antigen targeted by immunotherapy for melanoma patients. Expression of CDw60 by keratinocytes is defined by the presence of T-helper cell (Th)1 vs. Th2 cytokines, and can serve as a sentinel molecule to characterize an ongoing skin immune response. OBJECTIVES: These immunobiological characteristics have provided the incentive to study the expression of CDw60 in the context of progressive vitiligo. METHODS: Frozen sections were obtained from control skin and from vitiligo lesions and immunostained to show CDw60. Cells were cultured, their CDw60 expression studied and ribonuclease protection assays run to detect cytokine mRNA. RESULTS: Resistance to cytokine-mediated regulation of CDw60 expression was demonstrated in vitro by melanocytes, which appeared capable of generating autocrine and paracrine regulatory molecules supporting CDw60 expression. Induction of CDw60 expression was inhibited by antibodies to interleukin (IL)-4, suggesting that this cytokine was responsible, at least in part, for melanocyte-induced CDw60 expression. Marginal skin from patients with progressive generalized vitiligo consistently showed a reduction in epidermal CDw60 expression alongside elevated human leucocyte associated antigen (HLA)-DR expression at the margin. It thus appears that inflammatory infiltrates present in marginal skin generate type 1 rather than type 2 cytokines, supportive of a cell-mediated autoimmune response. CONCLUSIONS: These results support an active role of melanocytes within the skin immune system, and associate their loss in generalized vitiligo with a cell-mediated immune response mediated by type 1 cytokines.     

单唾液酸四已糖神经节苷脂钠注射液联合中药治疗糖尿病神经病变患者的临床疗效

[目的]探讨单唾液酸四已糖神经节苷脂钠注射液联合中药治疗糖尿病周围神经病变(DNP)的临床疗效。[方法]选取2009年6月～2010年6月某院收治的DNP患者60例,按随机数字表法分为观察组和对照组。对照组给予单唾液酸四已糖神经节苷脂钠注射液,观察组在此基础上加用中药。观察两组神经传导速度变化、临床疗效和不良反应。[结果]两组治疗后正中神经和腓总神经的MCV、SCV均显著升高(P﹤0.05),观察组较对照组升高更为显著(P﹤0.05);观察组总有效率为90.0%(27/30),对照组为66.7%(20/30),差异有统计学意义(P﹤0.05);两组均未发生不良反应。[结论]单唾液酸四已糖神经节苷脂钠注射液联合中药治疗DNP能显著提高疗效,无不良反应,值得临床推广应用。     

Gangliosides stabilize ionic homeostasis in rat cortical synaptosomes exposed to toxic concentrations of glutamate

Glutamate significantly increased intracellular calcium concentration, enhanced⁴⁵Ca²⁺ entry, and activated Na⁺/Ca²⁺ exchanger in synaptosomes from rat cerebral cortex. Preincubation with GM₁ ganglioside reduced the glutamate-induced increase in intracellular calcium and⁴⁵Ca²⁺ entry. Gangliosides and glutamate stimulated Na⁺/Ca²⁺ exchanger showing additive effects.